(i) Field of the Invention
The present invention relates to novel adjuvants for vaccine compositions, and to compositions comprising at least one antigen, in particular an antigen of viral, bacterial or parasitic origin, and at least one adjuvant.
(ii) Description of the Related Art
The development of inactivated vaccines or vaccines containing purified antigens is increasingly significant, since it makes it possible to avoid adverse side effects. However, the improvement in the quality of the antigens occurs to the detriment of their immunogenic nature. It is for this reason that they are combined with adjuvants of immunity.
Adjuvants of immunity are products which increase the reactions of the immune system, when they are administered in the presence of antigens of viral, bacterial or synthetic origin. They cause a massive appearance of macrophages at the site of injection, and then in the lymph nodes, increase the production of specific immunoglobulins, antibodies, and stimulate many cells involved in immune defense mechanism.
These adjuvants are diverse in nature. They can, for example, consist of liposomes or emulsions.
Very effective Freund's adjuvants: they result from the combination of a mineral oil and of a mannitol ester, possibly containing a killed mycobacterium. Vaccines prepared by mixing in equal parts a Freund's adjuvant with an aqueous antigenic medium are still used as standards throughout the world for laboratory studies. They are in the form of water in oil (W/O) emulsions, i.e., emulsions in which the continuous phase is the oil. These emulsions are very viscous; they are thus difficult to inject; they are also relatively unstable, since phase displacements are observed only a few days after their preparation.
By way of ordinary adjuvants, there are also metal salts, such as aluminum hydroxide, cerium nitrate, zinc sulphate, colloidal iron hydroxide or calcium chloride. Of these, aluminum hydroxide is the most commonly used. These adjuvants are described in the article by Rajesh K. Gupta et al., “Adjuvants, balance between toxicity and adjuvanticity” Vaccine, Vol. 11, Issue 3, 1993, pages 993-1006. They exhibit, however, weak immunostimulatory effectiveness, and sometimes induce, when these therapeutic compositions are injected, the formation of lesions and other local reactions, such as granulomas, at the point of injection.
More recently, it has been discovered that water-soluble salts of divalent or trivalent metals are good adjuvants of immunity, in particular manganese gluconate, calcium gluconate, manganese glycerophosphate, soluble aluminum acetate and aluminum salicylate. Such adjuvants are described in the international patent applications published under the numbers WO 96/32964 and WO 98/17311.
As other adjuvants of immunity, in particular in the case of mucosal administration, mention may be made of the sympathomimetic compounds described in the international patent application published under the number WO 98/15288.